The biological regulation of certain cellular functions has been shown to be closely associated with changes that occur in one of the two cyclic nucleotides cyclic 3'5' guanosine monophosphate (cGMP) and cyclic 3'5' adenosine monophosphate (cAMP), and it has been postulated that the actions of cyclic GMP and cyclic AMP provide opposing regulatory influence on a number of cellular processes. This concept has been termed by Goldberg and coworkers the "Yin Yang" hypothesis of biological control. The objectives of the proposed research are to investigate in vitro and in vivo the role that cyclic nucleotides may have in modulating human polymorphonuclear leukocyte function and the inflammatory response. The effect of the parent cyclophosphates and compounds known to increase the intracellular concentrations of these agents on neutrophil chemotactic, phagocytic and bactericidal activity will be determined in vitro. In addition, compounds which have been shown to be safe for use in humans will be studied for their effect on these functions in vivo. The changes that are induced in the intracellular concentrations of cyclic GMP and cyclic AMP in the neutrophils of patients with chemotactic, phagocytic and bactericidal defects will be monitored to determine if these functional defects can be attributed to alterations in the metabolism of the cyclic nucleotides. Attempts will then be made to correct abnormalities in neutrophil function by altering cyclic nucleotide concentrations in these cells in vitro and in vivo.